IL-37 relieves allergic inflammation by inhibiting the CCL11 signaling pathway in a mouse model of allergic rhinitis

Allergic rhinitis (AR) is the allergic inflammation of immune cells in the nasal mucosa, caused by an abnormal T-cell response. Interleukin (IL)-37, a unique member of the IL-1 family with broad anti-inflammatory roles in various autoimmune diseases, participates in the immune regulation of AR. However, the regulatory mechanism of IL-37 in AR has remained elusive. In the present study, a mouse model of AR was established by treating mice with ovalbumin (OVA). Following systemic administration of IL-37, the effects of the cytokine on allergic symptoms were evaluated. The nasal mucosal infiltration of eosinophils was assessed by histopathological observation. The serum and nasal lavage fluid concentrations of immunoglobulin (Ig)E, IgG1, IgG2a, interferon (IFN)-gamma, IL-4, IL-13, IL-17a and C-C motif cytokine ligand (CCL)11 were determined by ELISA. Treatment with OVA resulted in allergic symptoms, including enhanced eosinophil infiltration in the nasal mucosa, increased thickness of the nasal mucosa and increased levels of IgE, IgG1, IgG2a, IL-4, IL-13, IL-17a and CCL11, but the level of IFN-gamma was indicated to decrease. After IL-37 treatment, the frequency of nasal rubbing and sneezing was reduced compared with that in the OVA group. IL-37 administration also decreased the number of eosinophils in the nasal mucosa and the thickness of the nasal mucosa, as well as the serum and nasal lavage fluid levels of IgE, IgG1, IgG2a, IL-4, IL-13, IL-17a and CCL11, but the level of IFN-gamma decreased. In addition, the OVA-induced increases in histamine and substance P levels were reversed by IL-37 administration. CCL11 expression levels were correlated with the expression levels of IFN-gamma, IL-4, IL-13, IL-17a, histamine and substance P. In conclusion, IL-37 alleviated the OVA-induced allergic symptoms and allergic inflammatory response by reducing the serum cytokine levels via decreasing CCL11 expression levels in mice.